Despite improved preventive efforts, genital Chlamydia trachomatis infection remains the most common bacterial STD in the United States and is a global public health concern. If untreated, Chlamydia may persist allowing for transmission to uninfected individuals and possible clinical progression to complications. Recent reports studying chlamydia-infected patients between the time of routine testing (screening) and the time they returned for therapy demonstrated evidence of spontaneous clearance of a portion of untreated infections, suggesting immune-mediated clearance of chlamydia. Other than limited observations such as these, most of our knowledge on the host response to C. trachomatis has been derived from animal models and in vitro studies, which have demonstrated the importance of both cell-mediated and humoral-mediated immune responses to C. trachomatis. To assess the role of cell-mediated and humoral-mediated immune responses in clearance of genital chlamydia in humans, we propose a prospective pilot study that will enroll STD clinic patients with positive chlamydia screening tests that return for therapy. Study aims are: (1) determine the percentage of patients who spontaneously clear chlamydia versus having persisting infection by culture upon return for therapy and the relationship of patient age to this outcome; (2) measure proinflammatory and anti-inflammatory cytokines and cytokine gene expression in genital specimens from both patient groups by ELISA, cDNA Gene Array, or RT-PCR; and (3) measure anti-C, trachomatis antibody subtypes in the serum and genital secretions in both groups by ELISA. The relationship of specific immune responses to outcome in chlamydia (resolution versus persisting infection) will be analyzed through parametric or nonparametric methods and multivariate analysis. Study findings will provide preliminary data for further NIH grant applications, which if granted will allow continued enrollment of patients for this prospective study (increasing the sample size and power to detect outcomes) and the ability to test for additional host immune parameters. Findings from this research may improve our understanding of the host pathogen interactions in genital chlamydia and may provide the basis for future efforts towards prevention and control of genital chlamydia in development of novel immune interventions or a vaccine.